1. The N-terminus of survivin is a mitochondrial-targeting sequence and Src regulator
- Author
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Dunajová, Lucia, Cash, Emily, Markus, Robert, Rochette, Sophie, Townley, Amelia R., and Wheatley, Sally P.
- Subjects
C-Src ,Survivin ,Green Fluorescent Proteins ,Short Report ,Protein Sorting Signals ,Mitochondria ,Inhibitor of Apoptosis Proteins ,Structure-Activity Relationship ,src-Family Kinases ,Cell Adhesion ,Humans ,Amino Acid Sequence ,Src ,Cancer ,HeLa Cells - Abstract
Survivin (also known as BIRC5) is a cancer-associated protein that exists in several locations in the cell. Its cytoplasmic residence in interphase cells is governed by CRM1 (also known as XPO1)-mediated nuclear exportation, and its localisation during mitosis to the centromeres and midzone microtubules is that of a canonical chromosomal passenger protein. In addition to these well-established locations, survivin is also a mitochondrial protein, but how it gets there and its function therein is presently unclear. Here, we show that the first ten amino acids at the N-terminus of survivin are sufficient to target GFP to the mitochondria in vivo, and ectopic expression of this decapeptide decreases cell adhesion and accelerates proliferation. The data support a signalling mechanism in which this decapeptide regulates the tyrosine kinase Src, leading to reduced focal adhesion plaques and disruption of F-actin organisation. This strongly suggests that the N-terminus of survivin is a mitochondrial-targeting sequence that regulates Src, and that survivin acts in concert with Src to promote tumorigenesis., Summary: The proline-rich N-terminal ten amino acids of survivin is a mitochondrial-targeting domain and a regulator of the proto-oncogene Src. Hence, survivin could act in concert with Src to promote tumorigenesis.
- Published
- 2016